ObjectiveThe aim of the study was to find out the predictive value of single monotic auditory steady-state response (ASSR) for hearing threshold estimation in children with severe to profound sensorineural hearing loss (SNHL).MethodologyForty-eight children (96 ears) with severe to profound SNHL were included in the present study, with age range 1-10 years. They were subjected to age-based audiological evaluation to estimate the behavioral thresholds. Single monotic ASSR was performed for all children using test signals of 250, 500, 1000, 2000, and 4000 Hz, modulated in both ears at high rates of 67, 74, 81, 88, and 95 Hz, respectively, using GSI Audera-evoked potential system. ASSR thresholds were obtained and analyzed according to the equipment default criteria.ResultsThe number and percentage of ASSR detected were highest at 1000 Hz then 500 Hz followed by 2000 Hz and were the least at 4000 and 250 Hz in all children. The ASSR thresholds obtained were statistically correlated with the behavioral pure tone audiometry thresholds at 500, 100, and 2000 Hz. A considerable number of ears with no sound field thresholds or click auditory brainstem response responses showed ASSR.ConclusionSingle monotic ASSR, with high modulation frequencies, has proven to be a reasonable method for estimating hearing sensitivity in the mid-conventional audiometric frequencies in children with severe to profound SNHL.RecommendationsAll children with no behavioral hearing threshold and/or absent click-evoked auditory brainstem response should be tested by ASSR at 500, 1000, and 2000 Hz to give information about the presence of useful residual hearing. ASSR can provide important information for use in the cochlear implant selection process

Auditory steady-state response (ASSR) audiometry is a commercially available tool that is used to predict behavioral auditory threshold. Its particular value stems from its ability to measure frequency-specific responses in the background electroencephalogram (EEG) to auditory stimuli presented across a broad range of frequencies and sound pressure levels [1].

Several attractive attributes have been reported in the clinical applications of ASSR. First, the test stimuli, while not being pure tones, are reasonably frequency-specific regardless of the mode of modulation. Second, the stimuli are continuous, making the calibration straightforward [2]. Third, ASSR measurement facilitates the assessment of patients with severe to profound degree of sensorineural hearing loss (SNHL) [3]. The steady tonal stimuli used in ASSR permit higher outputs to be realized than do typical evoked response test systems. Fourth, multiple frequencies and/or two ears can be tested simultaneously. Finally, the most important advantage is that the spectrum of the response is predicted precisely by that of the stimulus spectrum without the need of subjective interpretation of the recorded response. Hence, the common limitation of most clinical tests of auditory-evoked potentials is overcome [4].

The auditory brainstem response (ABR) cannot differentiate between severe and profound SNHL [5], whereas the ASSR can provide threshold information in a frequency-specific manner at intensity levels of 120 dB and higher. This intensity stimulation advantage uniquely qualifies the ASSR for investigation of residual hearing in young and difficult-to-test cochlear implant candidates [3].

ASSR was extensively studied in adults with severe to profound SNHL by many researchers [6-9]. Many researchers advised and recommended that ASSR in adults could not be simply implemented in children [10-12]. Nevertheless, ASSR studies conducted on children with severe to profound SNHL are scarce. Accordingly, this study was designed to find out the predictive value of single monotic ASSR for hearing threshold estimation in children with severe to profound SNHL. The relationship between the behavioral hearing thresholds and the ASSR thresholds was explored in this group of children.

Methodology

Patients

A total number of 48 children (96 ears) were included in the present study. All study children should have an age range from 1 to 10 years, severe to profound SNHL (hearing threshold equal to or more than 70 dBHL for octave frequencies between 250 and 8000 Hz), and normal middle ear function. All children were recruited Hearing and Speech Institute. Verbal consent was obtained from all the parents of children before contribution in the study.

Air conduction testing was performed starting at 1000 Hz then at 2000, 4000, 8000, 250, and 500 Hz using pure tones stimuli in a descending order to reach threshold, in addition to bone conduction testing from 500 to 4000 Hz. The method of threshold estimation, dependent on the child cooperation, was either conditioned play audiometry [13] or voluntary thresholds [14].

(b) Children below 3 years or uncooperative children who failed to perform (a) underwent the following:

(i) Behavioral observation audiometry: The children's response behavior was determined using warble tones and narrow band noise delivered through loudspeakers presented and calibrated at 45 azimuth. The maximum intensities for these stimuli were 85 dBHL for the tested frequencies 0.25, 0.5, 1, 2, and 4 kHz [15]. Response behavior seen during testing was either attention (increased and decreased motion, searching, localizing, listening) or reflex (head or limb reflex, eye blink).

(ii) ABR: ABR was performed for children while sleeping using the GSI Audera - Grason-Stadler-evoked potential system (USA) in a single-walled sound-treated room. Two-channel recordings consisted of positive recording from Fpz, negative from ipsilateral mastoid, and a ground on the forehead. Interelectrode impedance was adjusted to be no more than 5000 Ω.

The stimuli used were rarefaction acoustic clicks delivered through insert phone at intensity level of 90 dB nHL and at a repetition rate of 21.1 pulses/s. The response was filtered between 30 and 1500 Hz, amplified 100 000 times, recorded over 12 ms time window, and 1144 sweeps were averaged for each run. ABR wave V was traced down to threshold in 10 dB descending steps and its latency was estimated. A threshold was defined as the lowest intensity level at which a response could be detected.

For the two age groups, speech audiometry was performed according to the vocabulary of the child in the form of speech reception threshold using Arabic spondee words [16] or digits in Arabic language or speech detection threshold [17].

(3) ASSR: Single monotic ASSR was applied for all children of the study group using the two-channel GSI Audera-evoked potential system. The test situation and the electrode montage were as described in ABR testing previously. The duration of testing for each child was 45 min.

The ASSR test stimuli were modulated pure tones presented by GSI TIP50 insert earphones (Grason Stadler, USA) with foam earplugs. The test protocol applied was the default test set for children aged less than 10 years. The used test signals were 250, 500, 1000, 2000, and 4000 Hz, modulated in both ears at high rates of 67, 74, 81, 88, and 95 Hz, respectively. High modulation rates were used to ensure that a satisfactory signal-to-noise ratio would exist for detection of responses during sleep or sedation. Each signal is amplitude and frequency modulated and individually presented to each ear. An amplitude modulation depth of 100% and frequency modulation width of 10% of the carrier tone was used to maximize the response amplitude [18].

ASSRs were initially obtained at the maximum sound levels of 106 dBHL for the 250 Hz carrier, 120 dBHL for the 1000 Hz, 117 dBHL for the 2000 Hz, and 115 dBHL for the 500 and 4000 Hz carrier frequencies. To estimate the ASSR thresholds, the level of the stimulus was decreased in 10 dB steps until the response could no longer be detected. It was then increased in 5 dB steps until the response was detected. On occasions where no ASSR was obtained at the maximum presentation level, the run was performed once.

ASSR analysis was performed as described by Cohen et al.[18]. The raw electroencephalogram was passed through a preamplifier, band pass filtered (10-500 Hz), and then Fourier analyzed at the stimulus modulation frequency to extract response phase and amplitude information. The presence or absence of a response was then determined automatically with a statistical detection criterion based on phase coherence, which looked for nonrandom phase behavior at which the system calculated the probability that a set of observed phase angles could occur in the absence of a response.

The default criterion for the GSI Audera-evoked potential system considered a response to be present when the probability was sufficiently small (P < 0.01). A test run was terminated either when the statistical criterion was reached (after a minimum of 16 samples) or after 64 samples if the criterion had not been reached. The duration of a single recording ranged from 22 to 89 s. This maximum duration of up to 89 s is standard protocol for the statistical analysis performed by the Audera system.

The Audera system has three result options: (a) phase-locked result - if a significant response is found regardless of the noise level, (b) random result - when no response is found and the EEG does not exceed the noise threshold level, and (c) noise result - when no response is found after 64 samples and when the EEG exceeds the noise threshold limit. All results of the system are displayed in [Figure 1].

Figure 1: The three result options of GSI Audera in the form of phase locked, random, and noise

ASSR threshold was defined as the lowest level at which a statistically significant response could be obtained (phase locked) and for which the next lowest presentation level showed no response (random). 'Noise' results are not included in the threshold determination process. Once ASSR thresholds have been established over a number of frequencies, the software provided the option to extrapolate from these results the patient's estimated behavioral audiogram [6].

Data analysis

The collected data were coded, tabulated, and statistically analyzed using statistical package for social sciences software (SPSS), version 18.0. Simple descriptive statistics were performed to calculate numerical parametric data, such as mean, SD, and minimum/maximum of the range. Inferential analyses were performed for quantitative variables using the paired t-test in patients of two dependent groups with parametric data. For qualitative data, inferential analyses were performed using the χ2 -test for paired categorical data. The level of significance was taken at P value less than 0.05.

Results

The study group children (n = 48) comprised 25 boys (52.1%) and 23 girls (47.9%). Their mean age was 3.9 years (SD ± 1.9) with a range of 1.5-10 years. According to the age, all children were divided into two subgroups: subgroup 1 included 28 children with at least 3 years of age (n = 56 ears) with mean age of 4.9 ± 1.8 SD and subgroup 2 included 20 children less than 3 years of age (n = 40 ears) with mean age of 2.4 ± 0.8 SD.

Results of subgroup 1

As shown in [Table 1] and [Figure 2], the pure tone audiometry (PTA) thresholds were in the severe to profound category of SNHL. Notably, the number of ears with PTA threshold responses decreased with the increase in tested frequency.

In subgroup 1, the number and percentage of ASSR detected were highest at 1000 Hz then 500 Hz followed by 2000 Hz and were the least at 4000 and 250 Hz [Figure 3]. Considering the mean ASSR thresholds, no statistically significant difference existed between the right and left ears with respect to ASSR thresholds at different frequencies [Table 2].

Table 2 Mean, SD, paired t-test, and P value of ASSR from the right and left ears in subgroup 1

In subgroup 2, the majority of sound field responses were obtained at lower frequencies. A large percentage of ears around 75 and 85% did not show sound field responses at 2 and 4 kHz, respectively [Table 4]. An absent click ABR at 100 dB nHL was detected in 90% of ears (n = 36) of children confirming severe to profound SNHL. Only three ears showed ABR response at 80 dB nHL and one ear at 90 dB nHL.

Similar to subgroup 1, the number and percentage of ASSR detected were highest at 1000 Hz then 2000 Hz followed by 500 Hz and were the least at 4000 and 250 Hz [Table 5]. No statistically significant difference existed between the right and left ear ASSR thresholds. The difference between the better ear sound field thresholds and ASSR reached up to 24.3 ± 9, 26.9 ± 8.5, 22.7 ± 4.6, 22.8 ± 11.1, and 23.3 ± 7.6 at 0.25, 0.5, 1, 2, and 4 kHz, respectively [Table 6].

Analysis of the ASSR in ears with no sound field response at different frequencies was made. In ears with no sound field response, ASSR was detected at 2 kHz (47% of ears gave ASSR) followed by 1 kHz (39% of ears), 4 kHz (27% of ears) then 0.5 kHz (8% of ears), whereas 0.25 kHz did not give ASSR in those ears [Table 7]. Moreover, the detectability of ASSR at 2 and 4 kHz in ears with no click ABR response at 100 dB nHL in children of subgroup 2 was in 53% (n = 19) and 25% (n = 9) at 2 and 4 kHz, respectively, at an average intensity of 112 dBHL.

Table 7 ASSR in ears with no sound field response at different frequencies

Forty-eight children with severe to profound SNHL were tested by single monotic ASSR using GSI Audera to determine its value as an objective clinical test in detecting hearing thresholds compared with behavioral subjective measures.

Analysis of the results of ASSR in study subgroups showed that the mid frequencies (500, 1000, and 2000 Hz) had the greatest percent detection of the response, whereas 250 and 4000 Hz showed the least response detection [Figure 3], [Table 5]). One of the explanations for such difference in response detection across frequencies might be related to the maximum stimulation intensity across frequencies provided by the equipment. It is highest at 1 kHz (120 dBHL) and lowest at 0.25 kHz (106 dBHL). The absence of the response at 4 kHz in a large number of children could be related to the severity of the hearing loss in the group studied at this particular frequency.

This is in agreement with the study by Ahn et al.[19] who found that the largest percentage of absent ASSR was at 4 kHz (31.6% of ears) in adult patients with severe to profound SNHL. In a study by Swanepoel et al. [20] on 15 children with severe to profound SNHL, the largest responses of ASSR obtained were at 2 kHz followed by 1, 4 kHz then finally at 0.5 kHz.

The difference between ASSR thresholds and behavioral thresholds was greater at the lower frequencies (0.25 and 0.5 kHz) compared with mid and higher frequencies. Stapells and Van Maanen [21] emphasized that the difference in thresholds between the behavioral measures and ASSR in children with severe to profound SNHL depends on the ASSR technique used. This was attributed to the lack of standardization among systems. Using single monotic ASSR, Bosman [22] found mean differences of 30, 18, 20, and 17 dB at 0.5, 1, 2, and 4 kHz, respectively. In contrast, lesser differences of 6 ± 10, 4 ± 8, 4 ± 9, and 4 ± 12 dB for frequencies 0.5, 1, 2, and 4 kHz were obtained by Swanepoel et al. [20] when tested by dichotic single frequency ASSR. Moreover, Herdman and Stapells [11] used MASTER technique and reported a difference within 5-16 dB of behavioral thresholds for 500, 1000, 2000, and 4000 Hz.

The larger difference obtained in this study when using the single monotic ASSR (GSI, Audera) may be related to the number of harmonic overtones. The GSI Audera only takes account of the first overtone, whereas the other ASSR systems study phase and amplitude of a number of harmonic overtones. When several overtones are studied, additional information can be gathered, and therefore more reliable or lower ASSR thresholds can be obtained [23].

Another factor that could be related to the GSI Audera is its sensitivity to background interferences. These might lengthen the recording time up to 60 min per child [8]. In contrast, the multiple dichotic ASSR takes only 15 min recording time per run while estimating eight frequencies simultaneously in both ears [24].

An additional factor contributed to the increased differences between sound field thresholds and ASSR in subgroup 2. It was related to the limits of loudspeaker used in the sound field facility (85 dB) missing children in the profound degree. This lowered the response detection of ASSR in this group compared with subgroup 1. The ASSR in subgroup 2 provided a stimulation level up to 106-120 dBHL. This implied the importance of a technique such as the ASSR, which can provide threshold data for profoundly deaf infants and children.

However, Rodrigues et al. [25] found significantly small differences between multiple dichotic ASSR and the visual reinforcement audiometry in a group of children with a mean age of 16 months with cochlear hearing loss.

Despite these shortcomings, a single frequency ASSR per ear (used in this study) was suggested in patients with severe to profound SNHL to eliminate the possible interactions between multiple stimuli when applied at high intensities. Intensity levels above 60 dB sound pressure level may contaminate the accuracy of responses [26].

Picton et al. [27] stated that the closer ASSR thresholds to behavioral thresholds using monotic single ASSR in profound hearing loss category can be attributed to the loudness recruitment and the limited dynamic range of residual hearing. The basic idea of recruitment is that the response increases in amplitude more quickly with increasing intensity in patients with SNHL. This would make it easier to recognize the response at intensities close to behavioral thresholds [28].

In contrast, in children with normal hearing, Luts and Wouters [12] reported a mean ASSR thresholds for normal hearing infants at an average corrected age of 12 days equal to 42 ± 10, 35 ± 10, 32 ± 10, and 36 ± 9 dBHL for 0.5, 1, 2, and 4 kHz, respectively. Compared with adults, these thresholds were elevated by an average of 11 dB. Using multiple ASSR, the thresholds obtained were 36, 30, 24, and 15 dBHL at 500, 1000, 2000, and 4000 Hz, respectively, with no differences in the results of younger versus older infants as studied by Van Maanen and Stapells [29]. Moreover, Savio et al. [10] estimated the physiologic behavioral difference when using ASSR around 56, 52, 50, and 50 dB at 500, 1000, 2000, and 4000 Hz, respectively.

There are many factors that contribute to the variability seen across ASSR studies in the literature. Studies that include patients with regions of normal hearing may show higher means and SDs than studies that include patients with greater amounts of hearing loss. There are also several major differences between studies in terms of methodology. Studies differ in the use of single versus multiple frequency stimulation, high versus low modulation rates, AM versus AM/FM stimuli, the statistical detection method, recording duration, the amount and type of averaging, and the definition of threshold [11].

The statistically significant correlation observed in subgroup 1 between PTA thresholds and ASSR thresholds [Table 3] is in agreement with the study by Ghannoum et al. [9]. They studied adults with severe to profound group of hearing loss and found that the best correlations between PTA and ASSR thresholds were present at 500 Hz, 1, 2, and 4 kHz. Similarly, the behavioral and ASSR thresholds for 1000, 2000, and 4000 Hz were highly correlated (with the lowest correlation at 500 Hz) in a study by Herdman and Stapells [11]. The best correlations between PTA and ASSR thresholds obtained by Canale et al. [7] and Ghannoum et al. [9] were at 1000 and 2000 Hz.

The reduced correlation between ASSR and PTA at 4 kHz found in the current study was also reported by Herdman and Stapells [11], Dimitrijevic et al. [28], Swanepoel et al. [20], Picton et al. (2005) [27], and Ahn et al. [19]. However, the explanation of such finding was not clear across studies.

Considering the ASSR at low frequencies of 0.25 and 0.5 kHz in this study, an increased difference between behavioral thresholds and estimated ASSR values was observed in addition to the reduced correlation particularly at 250 Hz. Similar findings were reported by Perez-Abalo et al. [24], Dimitrijevic et al. [28], and Luts and Wouters [12]. This was explained on the basis of neural synchrony. There is likely longer latency in the neurons responding to the low frequency sounds caused by the broader region of activation on the basilar membrane. This decreases the time locked summation of the responses [6].

Another explanation by Rance et al. [3] was that low-frequency stimuli (0.25 kHz) at high intensities might result in somatosensory rather than auditory responses. The problem in estimating 0.25 kHz ASSR thresholds could result from the low-frequency evoked response, which has a greater intrinsic jitter due to neural asynchrony. This might explain the relative difficulty in threshold detection compared with the higher test frequencies.

From the aforementioned discussion, it can be concluded that the 250 Hz hearing threshold detection is still solely based on behavioral estimation (sound field testing in infants), which is in support for the reliability of sound field testing at 250 Hz - the findings showed in this study. In group 2, all ears (100%) with absent sound field response at 250 Hz had absent ASSR [Table 7]. The importance of detecting hearing threshold at 250 Hz in children stems from its role in hearing aid adjustment and subsequent response satisfaction.

The determination of profound SNHL in children is challenging [30]. In subgroup 2, the percentage of children with residual hearing thresholds unmeasurable with sound field testing was 30, 30, 45, 75, and 85 for 0.25, 0.5, 1, 2, and 4 kHz, respectively. The responses to click ABR were only detected in 10% of subgroup 2 children. However, when using single monotic ASSR, a considerable percentage of ears showed ASSR responses in particular at 1, 2, and 4 kHz. Compared with click ABR, ASSR was obtained in 53 and 25% of children with absent ABR at 2 and 4 kHz, respectively.

This confirmed that the absence of ABR and behavioral sound field stimulation thresholds does not rule out the presence of residual hearing, which may be measured using the ASSR. Similarly, a high percentage of ASSR detection in absence of click ABR was reported by Stueve and O'Rourke [31] with an average threshold at 110 dBHL. ASSR can be a primary source of information regarding profound levels of hearing loss as suggested by Swanepoel et al. [20].

Many studies compared ASSR and click ABR thresholds for infants and young children with different degrees of SNHL, and the results have indicated significant correlations between both techniques [12, 25, 31, 32].

Finally, the average time for the recording of monotic single ASSR thresholds in this study ranged from 30 to 60 min for each child. This duration was needed for threshold estimation at five frequencies (0.25, 0.5, 1, 2, and 4 kHz) sequentially at varying intensities (descending in 10 dB steps and ascending in 5 dB steps) in each ear separately in addition to the noisy recordings that were repeated. The preparation of the patients, electrode placement, impedance checks, stabilization of test environment, and the time of sedation were not included in the calculations. Herdman and Stapells [11] demonstrated that, when multifrequency stimuli was used binaurally, there was only a shortening of the measurement time. Roeser et al. [33] believed that the measurement time can be shortened by up to 50% if stimulation occurs in both ears simultaneously.

Canale et al. [7] demonstrated a mean time of 42 min for the whole measurement in both ears, with a variation of between 30 and 60 min. Swanepoel et al. [20] demonstrated a measurement time of 23 min and Perez-Abalo et al. [24] reported in their study a mean time of ˜21 min, with Audix (using multiple ASSR). Luts and Wouters [12] demonstrated an average time of 50 min for MASTER and 44 min for GSI Audera. Rance [34] reported that the average measurement time for ASSR measurements is 45-60 min. The long duration of ASSR testing limits its wide application, particularly in children.

In summary, the presence of ASSR thresholds at increased intensities not attainable with ABR and often not with behavioral measures in young children makes this technique uniquely suited to the evaluation of severe and profound hearing losses. Single monotic ASSR, with high modulation frequencies, has proven to be a reasonable method for estimating hearing sensitivity in the mid-conventional audiometric frequencies, and the sensitivity decreases for 0.25 and 4 kHz. Such objective results obtained using the ASSR can provide important information for use in the cochlear implant selection process, alerting clinicians to the possibility that an ear may have useful aided hearing. ASSR can be used in selecting hearing aids for infants and young children who cannot provide reliable behavioral thresholds. ASSR can be effectively used to evaluate hearing aid benefit in sleeping infants as ASSR is not affected by sleep in children. Moreover, the ASSR stimuli are not affected or distorted when presented through a sound field speaker or amplified using a hearing aid.

ABR and ASSR each contribute importantly, and rather uniquely, to the pediatric audiologic test battery. The relationship between the two techniques is not competitive but rather complementary. The authors recommend that, for infants with severe to profound SNHL, sound field should be applied first for detection of low frequencies thresholds followed by ABR to click stimuli. If there is no response to click ABR, the examiner should proceed to ASSR testing at 500, 1000, and 2000 Hz. The intensity should start from the maximum then decreasing in 5 dB until threshold is obtained, if any. Furthermore, multiple dichotic stimulation should be investigated in children with severe to profound SNHL to minimize the duration of testing. The role of CE chirp stimulus in ASSR deserves to be studied to increase the response detection especially close to threshold.

Acknowledgements

The authors appreciate the contribution and cooperation of the children's parents in the production of this study.

Bosman R. Threshold estimation in normal and impaired ears using auditory steady state responses university of Pretoria. Thesis for partial fullfilment of Master degree in communication pathology. Department of communication pathology. University of Pretoria- South Africa 2003.